Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells

Journal of Translational Medicine

Chunxiao Zhou²  Victoria L Bae-Jump²  Weiyuan Zhang³  Fang Song³  Leo Li-Ying Chan¹  Hannah M Jones²  Xiaoli Ma³  Jiandong Wang³ 

[1] Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence 01843, MA, USA;Department of Obstetrics and Gynecology, Division of Gynecological Oncology, University of North Carolina, Chapel Hill, NC, USA;Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China

关键词: Primary cell culture;    Therapeutics;    10058-F4;    c-Myc;    Ovarian cancer;   

Others  :  1148361
DOI  :  10.1186/s12967-014-0226-x

 received in 2014-02-18, accepted in 2014-08-05,  发布年份 2014

【 摘 要 】

Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. Our objective was to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian carcinoma cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using MTT assay, colony formation, flow cytometry and Annexin V FITC assays, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. Treatment with 10058-F4 reduced cellular ATP production and ROS levels in SKOV3 and Hey cells. Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. The response to 10058-F4 was independent the level of c-Myc protein over-expression in primary cultures of ovarian carcinoma. These novel findings suggest that the growth of ovarian cancer cells is dependent upon c-MYC activity and that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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